Qd. Li et Ct. Bever, GAMMA-INTERFERON-INDUCED INCREASES IN INTRACELLULAR CATHEPSIN-B ACTIVITY IN PMA PRIMED THP-1 CELLS ARE BLOCKED BY INHIBITORS OF PROTEIN-KINASE-C, Immunopharmacology and immunotoxicology, 18(3), 1996, pp. 375-396
Macrophage proteinases including cathepsin B (CB) are implicated in th
e tissue injury of inflammatory lesions. We have previously shown that
interferon-gamma (IFN-gamma) increases intracellular levels of the ly
sosomal proteinase, CB, in THP-1 cell primed with phorbol 12-myristate
13-acetate (PMA). We have now examined the role of protein kinase C (
PKC) in this effect. Following activation with PMA, the intracellular
CB activity was significantly increased in the presence of 500 U/ml IF
N-gamma. With the addition of protein kinase C (PKC) inhibitors bisind
olylmaleimide, staurosporine, H-7, or phloretin a reversal of the effe
ct of IFN-gamma was noted whereas the addition of the cyclic nucleotid
e-dependent protein kinase inhibitors HA 1004, H-8, H-89, or cAMP-Depe
ndent Protein Kinase (PKA) Inhibitor did not block the effect. Althoug
h diacylglycerol (DAG) did not replace PMA in the study, Diacylglycero
l Kinase Inhibitor induced a more pronounced augmentation and PKC depl
etion inhibited the effect. This suggests that a PKC-dependent pathway
is involved in the response of CB in PMA primed THP-1 cells to IFN-ga
mma.